Institute of Infection, Immunity and Inflammation

Prof Iain Morgan

Prof Iain M Morgan
  • Visiting Professor (Institute of Infection Immunity and Inflammation)

telephone: 01413303155
email: Iain.Morgan@glasgow.ac.uk


My group has identified cellular proteins and pathways that functionally interact with human papillomavirus replication, transcription and genome segregation functions. The ultimate purpose of our work is to increase our understanding of the viral life cycle and identify novel anti-viral targets with therapeutic potential. The viral protein HPV 16 E2 is an essential factor for regulating viral transcription, replication (in association with E1) and genome segregation. In replication, E2 binds to target DNA sequences surrounding the viral origin and recruits E1 via a protein-protein interaction. The E1 protein then recognises the viral origin and forms a di-hexameric helicase complex responsible for genome replication. In genome segregation, E2 associates with mitotic chromatin and the viral genome simultaneously allowing distribution of the viral genome into daughter cells following cell division. My lab has identified the cellular replication factor TopBP1 as a binding partner for E2 and using mutation screening demonstrated that this interaction is required for efficient E2-E1 mediated DNA replication and also for the association of E2 with mitotic chromatin. We have also demonstrated that TopBP1 interacts with E1 and evidence suggests a triple complex between E2-E1-TopBP1 that is required for optimum viral genome replication and we are currently testing this hypothesis. There are two crucial novel aspects to these observations; firstly that E2 regulates viral replication not simply by recruiting E1 but also by interacting with cellular proteins; and secondly that TopBP1 is the mitotic chromatin receptor for HPV16 E2.

Current collaborations on this project are with Dr Joanne Parish, University of St Andrews, where we are working towards a crystal structure for the E2-TopBP1 interaction; and with Professor Peter Howley, Harvard Medical School, where we are using advanced proteomic techniques to identify differences in replication complexes when E2 fails to bind to TopBP1.

The overall goal of these studies is to develop the E2-E1-TopBP1 complex as an anti-viral target and also to improve our understanding of the role of TopBP1 in replication in mammalian cells.

Jump to: 2013 | 2012 | 2011 | 2010 | 2009 | 2008 | 2007 | 2006 | 2005 | 2004 | 2003 | 2002 | 2001
Number of items: 31.

2013

Donaldson, M.M., Mackintosh, L.J., Bodily, J.M., Dornan, E.S., Laimins, L.A., and Morgan, I.M. (2013) An interaction between human papillomavirus 16 E2 and TopBP1is required for optimum viral DNA replication and episomal genome establishment. Journal of Virology . ISSN 0022-538X (doi:10.1128/JVI.01002-12) (In Press)

2012

Finlay, M., Yuan, Z., Morgan, I.M., Campo, M., and Nasir, L. (2012) Equine sarcoids: Bovine Papillomavirus type 1 transformed fibroblasts are sensitive to cisplatin and UVB induced apoptosis and show aberrant expression of p53. Veterinary Research , 43 . p. 81. ISSN 0928-4249 (doi:10.1186/1297-9716-43-81)

2011

King, L.E., Dornan, E.S., Donaldson, M.M., and Morgan, I.M. (2011) Human papillomavirus 16 E2 stability and transcriptional activation is enhanced by E1 via a direct protein–protein interaction. Virology, 414 (1). pp. 26-33. ISSN 0042-6822 (doi:10.1016/j.virol.2011.03.002)

2010

King, L.E., Fisk, J.C., Dornan, E.S., Donaldson, M.M., Melendy, T., and Morgan, I.M. (2010) Human papillomavirus E1 and E2 mediated DNA replication is not arrested by DNA damage signalling. Virology, 406 (1). pp. 95-102. ISSN 0042-6822 (doi:10.1016/j.virol.2010.06.033 )

Arendt, M. L., Nasir, L., and Morgan, I. M. (2010) The human and canine TERT promoters function equivalently in human and canine cells. Veterinary and Comparative Oncology, 8 (4). pp. 310-316. ISSN 1476-5810 (doi:10.1111/j.1476-5829.2010.00227.x)

Blackford, A.N. et al. (2010) Adenovirus 12 E4orf6 inhibits ATR activation by promoting TOPBP1 degradation. Proceedings of the National Academy of Sciences of the United States of America, 107 (27). pp. 12251-12256. ISSN 0027-8424 (doi:10.1073/pnas.0914605107)

2009

Arendt, M., Nasir, L., and Morgan, I.M. (2009) Oncolytic gene therapy for canine cancers: teaching old dog viruses new tricks. Veterinary and Comparative Oncology, 7 (3). pp. 153-161. ISSN 1476-5810 (doi:10.1111/j.1476-5829.2009.00187.x)

Arendt, M.L., Nasir, L., and Morgan, I.M. (2009) A novel two-step transcriptional activation system for gene therapy directed toward epithelial cells. Molecular Cancer Therapeutics, 8 (12). pp. 3244-3254. ISSN 1535-7163 (doi:10.1158/1535-7163.MCT-09-0543)

Finlay, M., Yuan, Z.Q., Burden, F., Trawford, A., Morgan, I.M., Campo, M.S., and Nasir, L. (2009) The detection of Bovine Papillomavirus type 1 DNA in flies. Virus Research, 144 (1-2). pp. 315-317. ISSN 0168-1702 (doi:10.1016/j.virusres.2009.04.015)

Gobeil, P.A.M., Yuan, Z.Q., Gault, E.A., Morgan, I.M., Campo, M.S., and Nasir, L. (2009) Small interfering RNA targeting bovine papillomavirus type 1 E2 induces apoptosis in equine sarcoid transformed fibroblasts. Virus Research, 145 (1). pp. 162-165. ISSN 0168-1702 (doi:10.1016/j.virusres.2009.06.019)

Johansson, C., Graham, S.V., Dornan, E.S., and Morgan, I.M. (2009) The human papillomavirus 16 E2 protein is stabilised in S phase. Virology, 394 (2). pp. 194-199. ISSN 0042-6822 (doi:10.1016/j.virol.2009.08.046)

Morris, J.S., Nixon, C., King, O.J.A., Morgan, I.M., and Philbey, A.M. (2009) Expression of TopBP1 in canine mammary neoplasia in relation to histological type, Ki67, ER alpha and p53. Veterinary Journal, 179 (3). pp. 422-429. ISSN 1090-0233 (doi:10.1016/j.tvjl.2007.10.025)

2008

Arendt, M.L., Morris, J., Nasir, L., and Morgan, I.M. (2008) Abstracts presented at the ESVONC spring meeting, Cambridge, UK, 23-25 March 2007. Veterinary and Comparative Oncology, 6 (1). pp. 65-83. ISSN 1476-5810

Morris, J., Nixon, C., Bruck, A., Nasir, L., Morgan, I.M., and Philbey, A. (2008) Immunohistochemical expression of TopBP1 in feline mammary neoplasia in relation to histological grade, Ki67, ERα and p53. Veterinary Journal, 175 (2). pp. 218-226. ISSN 1090-0233 (doi:10.1016/j.tvjl.2007.01.006)

Morris, J.S., Nixon, C., Bruck, A., Nasir, L., Morgan, I.M., and Philbey, A. (2008) Immunohistochemical expression of TopBP1 in feline mammary neoplasia in relation to histological grade, Ki67, ERalpha and p53. Veterinary Journal, 175 (2). pp. 218-226. ISSN 1090-0233 (doi:10.1016/j.tvjl.2007.01.006 )

Morris, J.S., Nixon, Colin, Bruck, A., Nasir, L., Morgan, I.M., and Philbey, A. (2008) Immunohistochemical expression of TopBP1 in feline mammary neoplasia in relation to histological grade, Ki67, ER alpha and p53. Veterinary Journal, 175 (2). pp. 218-226. ISSN 1090-0233 (doi:10.1016/j.tvjl.2007.01.006)

2007

Going, J.J., Nixon, C., Dornan, E.S., Boner, W., Donaldson, M.M., and Morgan, I.M. (2007) Aberrant expression of TopBP1 in breast cancer. Histopathology, 50 (4). pp. 418-424. ISSN 0309-0167 (doi:10.1111/j.1365-2559.2007.02622.x)

Donaldson, M.M., Boner, W., and Morgan, I.M. (2007) TopBP1 regulates human papillomavirus type 16 E2 interaction with chromatin. Journal of Virology, 81 (8). pp. 4338-4342. ISSN 0022-538X (doi:10.1128/JVI.02353-06)

Gobeil, P., Gault, E.A., Campo, M.S., Gow, J., Morgan, I.M., and Nasir, L. (2007) Equine sarcoids are not induced by an infectious cell line. Equine Veterinary Journal, 39 . pp. 189-191. ISSN 0425-1644 (doi:10.2746/042516407X179879)

Nasir, L, Gault, E, Morgan, IM, Chambers, G, Ellsmore, V, and Campo, MS (2007) Identification and functional analysis of sequence variants in the long control region and the E2 open reading frame of bovine papillomavirus type 1 isolated from equine sarcoids. Virology, 364 . pp. 355-361. (doi:10.1016/j.virol.2007.02.019)

2006

Wright, R.H.G., Dornan, E.S., Donaldson, M.M., and Morgan, I.M. (2006) TopBP1 contains a transcriptional activation domain suppressed by two adjacent BRCT domains. Biochemical Journal, 400 . pp. 573-582. ISSN 0264-6021 (doi:10.1042/BJ20060831)

2005

Okoye, A., Cordano, P., Taylor, E.R., Morgan, I.M., Everett, R., and Campo, M.S. (2005) Human papillomavirus 16 L2 inhibits the transcriptional activation function, but not the DNA replication function, of HPV-16 E2. Virus Research, 108 (1). pp. 1-14. ISSN 0168-1702 (doi:10.1016/j.virusres.2004.07.004)

Morgan, I (2005) Detection and quantitation of HPV DNA replication by Southern blotting and real-time PCR. Methods in Molecular Medicine, 119 . pp. 349-362.

2004

McPhillips, MG, Veerapraditsin, T, Cumming, SA, Karali, D, Milligan, SG, Boner, W, Morgan, IM, and Graham, SV (2004) SF2/ASF binds the human papillomavirus type 16 late RNA control element and is regulated during differentiation of virus-infected epithelial cells. Journal of Virology, 78 . pp. 10598-10605. ISSN 0022-538X (doi:10.1128/JVI.78.19.10598-10605.2004)

2003

Taylor, ER, Boner, W, Dornan, ES, Corr, EM, and Morgan, IM (2003) UVB irradiation reduces the half-life and transactivation potential of the human papillomavirus 16 E2 protein. Oncogene, 22 . pp. 4469-4477. (doi:10.1038/sj.onc.1206746)

Taylor, ER, Dornan, ES, Boner, W, Connolly, JA, McNair, S, Kannouche, P, Lehmann, AR, and Morgan, IM (2003) The fidelity of HPV16 E1/E2-mediated DNA replication. Journal of Biological Chemistry, 278 . pp. 52223-52230. ISSN 0021-9258 (doi:10.1074/jbc.M308779200)

Taylor, ER, and Morgan, IM (2003) A novel technique with enhanced detection and quantitation of HPV-16 E1- and E2-mediated DNA replication. Virology, 315 . pp. 103-109. (doi:10.1016/S0042-6822(03)00588-9)

2002

Boner, W, and Morgan, IM (2002) Novel cellular interacting partners of the human papillomavirus 16 transcription/replication factor E2. Virus Research, 90 . pp. 113-118.

Boner, W, Taylor, ER, Tsirimonaki, E, Yamane, K, Campo, MS, and Morgan, IM (2002) A functional interaction between the human papillomavirus 16 transcription/replication factor E2 and the DNA damage response protein TopBP1. Journal of Biological Chemistry, 277 . pp. 22297-22303. ISSN 0021-9258 (doi:10.1074/jbc.M202163200)

2001

Beniston, R.G., Morgan, I.M., O'Brien, V., and Campo, M.S. (2001) Quercetin, E7 and p53 in papillomavirus oncogenic cell transformation. Carcinogenesis, 22 . pp. 1069-1076.

Vance, KW, Campo, MS, and Morgan, IM (2001) A novel silencer element in the bovine papillomavirus type 4 promoter represses the transcriptional response to papillomavirus E2 protein. Journal of Virology, 75 . pp. 2829-2838. ISSN 0022-538X

This list was generated on Fri May 17 17:45:25 2013 BST.

Grants and Awards listed are those received whilst working with the University of Glasgow.

  • Interaction between the essential replication factor TopBP1 and human papillomavirus 16 E1: a novel antiviral target
    Cancer Research UK
    2011 - 2014
     
  • Characterising a novel oncogenic mechanism of the major human viral carcinogen: human papillomavirus 16 (HPV16) E2 suppresses the p53 response
    Cancer Research UK
    2010 - 2012
     
  • Centre for Integrated Virology
    MRC
    2010 - 2015
     
  • Advanced proteomic analysis of human papillomavirus replication complexes
    Wellcome Trust
    2010 - 2010
     
  • The role of matrix metallo proteinase-1 (MMP-1) in the pathogenesis of equine sarcoids. A potential therapeutic target?
    Horserace Betting Levy Board
    2007 - 2011
     
  • TopBP1 as therapeutic target for human papillomavirus infection.
    Medical Research Scotland
    2007 - 2011
     
  • The role of matrix metallo proteinase-1 in the pathogenesis of equine sarcoids
    Wellcome Trust
    2007 - 2007
     
  • The role of human papillomaviruses and their oncoproteins in non melanoma skin cancer
    MRC
    2007 - 2011
     
  • Identification of TopBP1 target genes in normal and DNA damaged breast cancer cells
    Breast Cancer Campaign
    2007 - 2008
     
  • Study into the synergistic effects of non-steroidal anti-inflammatory drugs on telomerase activity in canine transitional cell carcinoma
    The Pet Plan Charitable Trust
    2007 - 2007
     
  • Strategic Partnership Equipment Grant
    MRC
    2007 - 2007
     
  • Research Council UK fellowship - molecular oncology
    EPSRC
    2006 - 2011
     
  • A therapeutic strategy for improving treatment of virally induced gynaecological cancers and pre-maglignant tumours
    Wellbeing of Women
    2006 - 2008
     
  • From viral genes to disease: understanding the function of bovine papillomavirus E2 proteins in sarcoid pathogenesis and inhibiting viral replication in sarcoid therapy.
    The Horse Trust
    2006 - 2009
     
  • Novel systems delivering targeted gene therapy for the treatment of canine cancers
    The Dogs Trust
    2005 - 2008
     
  • Investigating the role of the DNA repair protein TopBP1 in initiation of human papillomavirus DNA replication
    Cancer Research UK
    2004 - 2007
     
  • Identification of DNA elements regulating replication in mammalian cells
    BBSRC
    2003 - 2006